Mycobacterium tuberculosis 19-Kilodalton Lipoprotein Inhibits Mycobacterium smegmatis-Induced Cytokine Production by Human Macrophages In Vitro

AUTOR(ES)

Post, Frank A.

FONTE

American Society for Microbiology

RESUMO

Vaccination of mice with Mycobacterium vaccae or M. smegmatis induces some protection against M. tuberculosis challenge. The 19-kDa lipoprotein of M. tuberculosis, expressed in M. vaccae or M. smegmatis (M. smeg19kDa), abrogates this protective immunity. To investigate the mechanism of this suppression of immunity, human monocyte-derived macrophages (MDM) were infected with M. smeg19kDa. Infection resulted in reduced production of tumor necrosis factor alpha (TNF-α) (P < 0.01), interleukin-12 (IL-12) (P < 0.05), IL-6 (P < 0.05), and IL-10 (P < 0.05), compared to infection with M. smegmatis vector (M. smegV). Infection with M. smeg19kDa and with M. smegV had no differential effect on expression of costimulatory molecules on MDM, nor did it affect the proliferation of presensitized T cells cocultured with infected MDM. When MDM were infected with M. smegmatis expressing mutated forms of the 19-kDa lipoprotein, including non-O-glycosylated (M. smeg19NOG), nonsecreted (M. smeg19NS), and nonacylated (M. smeg19NA) variants, the reduced production of TNF-α or IL-12 was not observed. When the purified 19-kDa lipoprotein was added directly to cultures of infected monocytes, there was little effect on either induction of cytokine production or its inhibition. Thus, the immunosuppressive effect is dependent on glycosylated and acylated 19-kDa lipoprotein present in the phagosome containing the mycobacterium. These results suggest that the diminished protection against challenge with M. tuberculosis seen in mice vaccinated with M. smegmatis expressing the 19-kDa lipoprotein is the result of reduced TNF-α and IL-12 production, possibly leading to reduced induction of T-cell activation.

Documentos Relacionados

• Prolonged Toll-Like Receptor Signaling by Mycobacterium tuberculosis and Its 19-Kilodalton Lipoprotein Inhibits Gamma Interferon-Induced Regulation of Selected Genes in Macrophages
• The Mycobacterium tuberculosis 19-Kilodalton Lipoprotein Inhibits Gamma Interferon-Regulated HLA-DR and FcγR1 on Human Macrophages through Toll-Like Receptor 2
• Expression of the Mycobacterium tuberculosis 19-kilodalton antigen in Mycobacterium smegmatis: immunological analysis and evidence of glycosylation.
• Homologs of Mycobacterium leprae 18-kilodalton and Mycobacterium tuberculosis 19-kilodalton antigens in other mycobacteria.
• Inhibition of Major Histocompatibility Complex II Expression and Antigen Processing in Murine Alveolar Macrophages by Mycobacterium bovis BCG and the 19-Kilodalton Mycobacterial Lipoprotein